Neurofibromatosis-2 (NF2) is a dominantly inherited disease that results in the formation of a wide range of tumors in the nervous system and associated glial tissues. Recent studies have shown that the product of the NF2 tumor-suppressor gene is a novel member of the 4.1 protein superfamily called merlin. Functionally, many of these proteins appear to serve as connections between the cytoskeleton and cell membrane. While the identification of NF2/merlin as a member of the protein 4.1 superfamily has been of great interest, it has not yet led to a specific hypothesis regarding its cellular function or its role in tumor suppression. A Drosophila merlin homologue (Dmerlin) has been cloned and sequenced. The overall goal of this proposal is to use the strengths of the Drosophila system to identify the functions and interacting partners of merlin. Specifically, l plan to conduct (1) a structure/function analysis of Dmerlin and (2) perform screens to identify functionally and physically associated genes.